Epidemiology and fitness effects of wood mouse herpesvirus in a natural host population

Rodent gammaherpesviruses have become important models for understanding human herpesvirus diseases. In particular, interactions between murid herpesvirus 4 and Mus musculus (a non-natural host species) have been extensively studied under controlled laboratory conditions. However, several fundamental aspects of murine gammaherpesvirus biology are not well understood, including how these viruses are transmitted from host to host, and their impacts on host fitness under natural conditions. Here, we investigate the epidemiology of a gammaherpesvirus in free-living wood mice (Apodemus sylvaticus) and bank voles (Myodes glareolus) in a 2-year longitudinal study. Wood mouse herpesvirus (WMHV) was the only herpesvirus detected and occurred frequently in wood mice and also less commonly in bank voles. Strikingly, WMHV infection probability was highest in reproductively active, heavy male mice. Infection risk also showed a repeatable seasonal pattern, peaking in spring and declining through the summer. We show that this seasonal decline can be at least partly attributed to reduced recapture of WMHV-infected adults. These results suggest that male reproductive behaviours could provide an important natural route of transmission for these viruses. They also suggest that gammaherpesvirus infection may have significant detrimental effects in wild hosts, questioning the view that these viruses have limited impacts in natural, co-evolved host species

A Mathematics Pipeline to Student Success in Data Analytics through Course-Based Undergraduate Research

This paper reports on Data Analytics Research (DAR), a course-based undergraduate research experience (CURE) in which undergraduate students conduct data analysis research on open real- world problems for industry, university, and community clients. We describe how DAR, offered by the Mathematical Sciences Department at Rensselaer Polytechnic Institute (RPI), is an essential part of an early low-barrier pipeline into data analytics studies and careers for diverse students. Students first take a foundational course, typically Introduction to Data Mathematics, that teaches linear algebra, data analytics, and R programming simultaneously using a project-based learning (PBL) approach. Then in DAR, students work in teams on open applied data analytics research problems provided by the clients. We describe the DAR organization which is inspired in part by agile software development practices. Students meet for coaching sessions with instructors multiple times a week and present to clients frequently. In a fully remote format during the pandemic, the students continued to be highly successful and engaged in COVID-19 research producing significant results as indicated by deployed online applications, refereed papers, and conference presentations. Formal evaluation shows that the pipeline of the single on-ramp course followed by DAR addressing real-world problems with societal benefits is highly effective at developing students\u27 data analytics skills, advancing creative problem solvers who can work both independently and in teams, and attracting students to further studies and careers in data science

Mitochondrial DNA Copy Numbers in Pyramidal Neurons are Decreased and Mitochondrial Biogenesis Transcriptome Signaling is Disrupted in Alzheimer’s Disease Hippocampi

Alzheimer\u27s disease (AD) is the major cause of adult-onset dementia and is characterized in its pre-diagnostic stage by reduced cerebral cortical glucose metabolism and in later stages by reduced cortical oxygen uptake, implying reduced mitochondrial respiration. Using quantitative PCR we determined the mitochondrial DNA (mtDNA) gene copy numbers from multiple groups of 15 or 20 pyramidal neurons, GFAP(+) astrocytes and dentate granule neurons isolated using laser capture microdissection, and the relative expression of mitochondrial biogenesis (mitobiogenesis) genes in hippocampi from 10 AD and 9 control (CTL) cases. AD pyramidal but not dentate granule neurons had significantly reduced mtDNA copy numbers compared to CTL neurons. Pyramidal neuron mtDNA copy numbers in CTL, but not AD, positively correlated with cDNA levels of multiple mitobiogenesis genes. In CTL, but not in AD, hippocampal cDNA levels of PGC1α were positively correlated with multiple downstream mitobiogenesis factors. Mitochondrial DNA copy numbers in pyramidal neurons did not correlate with hippocampal Aβ1-42 levels. After 48 h exposure of H9 human neural stem cells to the neurotoxic fragment Aβ25-35, mtDNA copy numbers were not significantly altered. In summary, AD postmortem hippocampal pyramidal neurons have reduced mtDNA copy numbers. Mitochondrial biogenesis pathway signaling relationships are disrupted in AD, but are mostly preserved in CTL. Our findings implicate complex alterations of mitochondria-host cell relationships in AD

Structure and Metal Binding Properties of ZnuA, a Periplasmic Zinc Transporter from \u3cem\u3eEscherichia coli\u3c/em\u3e

ZnuA is the periplasmic Zn2+-binding protein associated with the high-affinity ATP-binding cassette ZnuABC transporter from Escherichia coli. Although several structures of ZnuA and its homologs have been determined, details regarding metal ion stoichiometry, affinity, and specificity as well as the mechanism of metal uptake and transfer remain unclear. The crystal structures of E. coli ZnuA (Eco-ZnuA) in the apo, Zn2+-bound, and Co2+-bound forms have been determined. ZnZnuA binds at least two metal ions. The first, observed previously in other structures, is coordinated tetrahedrally by Glu59, His60, His143, and His207. Replacement of Zn2+ with Co2+ results in almost identical coordination geometry at this site. The second metal binding site involves His224 and several yet to be identified residues from the His-rich loop that is unique to Zn2+ periplasmic metal binding receptors. Electron paramagnetic resonance and X-ray absorption spectroscopic data on CoZnuA provide additional insight into possible residues involved in this second site. The second site is also detected by metal analysis and circular dichroism (CD) titrations. Eco-ZnuA binds Zn2+ (estimated K d \u3c 20 nM), Co2+, Ni2+, Cu2+, Cu+, and Cd2+, but not Mn2+. Finally, conformational changes upon metal binding observed in the crystal structures together with fluorescence and CD data indicate that only Zn2+ substantially stabilizes ZnuA and might facilitate recognition of ZnuB and subsequent metal transfer

Selecting Outcomes to Ensure Pragmatic Trials Are Relevant to People Living with Dementia

Outcome measures for embedded pragmatic clinical trials (ePCTs) should reflect the lived experience of people living with dementia (PLWD) and their caregivers, yet patient‐ and caregiver‐reported outcomes (PCROs) are rarely available in large clinical and administrative data sources. Although pragmatic methods may lead to use of existing administrative data rather than new data collected directly from PLWD, interventions are truly impactful only when they change outcomes prioritized by PLWD and their caregivers. The Patient‐ and Caregiver‐Reported Outcomes Core (PCRO Core) of the IMbedded Pragmatic Alzheimer's Disease (AD) and AD‐Related Dementias Clinical Trials (IMPACT) Collaboratory aims to promote optimal use of outcomes relevant to PLWD and their caregivers in pragmatic trials. The PCRO Core will address key scientific challenges limiting outcome measurement, such as gaps in existing measures, methodologic constraints, and burdensome data capture. PCRO Core investigators will create a searchable library of AD/AD‐related dementias (ADRD) clinical outcome measures, including measures in existing data sources with potential for AD/ADRD ePCTs, and will support best practices in measure development, including pragmatic adaptation of PCROs. Working together with other Cores and Teams within the IMPACT Collaboratory, the PCRO Core will support investigators to select from existing outcome measures, and to innovate in methods for measurement and data capture. In the future, the work of the IMPACT Collaboratory may galvanize broader embedded use of outcomes that matter to PLWD and their care partners in large health system

Improved quantum circuits for elliptic curve discrete logarithms

We present improved quantum circuits for elliptic curve scalar multiplication, the most costly component in Shor's algorithm to compute discrete logarithms in elliptic curve groups. We optimize low-level components such as reversible integer and modular arithmetic through windowing techniques and more adaptive placement of uncomputing steps, and improve over previous quantum circuits for modular inversion by reformulating the binary Euclidean algorithm. Overall, we obtain an affine Weierstrass point addition circuit that has lower depth and uses fewer $T$ gates than previous circuits. While previous work mostly focuses on minimizing the total number of qubits, we present various trade-offs between different cost metrics including the number of qubits, circuit depth and $T$-gate count. Finally, we provide a full implementation of point addition in the Q# quantum programming language that allows unit tests and automatic quantum resource estimation for all components.Comment: 22 pages, to appear in: Int'l Conf. on Post-Quantum Cryptography (PQCrypto 2020

Dating of Bruises in Children: An Assessment of Physician Accuracy

Dating of Bruises in Methods. Children who presented to the emergency department of a children's hospital with accidental bruises of known age and origin had demographic data and information about their injury recorded. Historyblinded emergency pediatricians, other physicians, and trainees (fellows, residents, and medical students) independently examined the bruised area and recorded injury characteristics and age estimation and ranked characteristics that influenced their estimation. Results. Fifty children with accidental bruises were enrolled. Emergency pediatricians' accuracy of age estimation within 24 hours of actual age was 47.6%. Individual emergency pediatrician's accuracy ranged from 0% to 100%, and the interobserver reliability was poor ( ‫؍‬ ؊0.03). Accuracy within 24 hours of actual age was 29.4% for other physicians and 36.8% for trainees, which was similar to the emergency pediatricians. Observers reported using color primarily to estimate age, followed by tenderness and then swelling; however, none of these factors was significantly correlated with accuracy. Conclusions. Physician estimates of bruise age are highly inaccurate within 24 hours of the actual age of the injury. Large individual variability and poor interrater reliability also suggest that caution must be used when interpreting these estimates. This study supports earlier studies, urging extreme caution in estimating bruise age, even when such estimates are based on direct examination of the injured area. Pediatrics 2003;112:804 -807; children, bruising, abuse, emergency

A Detailed Observational Analysis of V1324 Sco, the Most Gamma-Ray Luminous Classical Nova to Date

It has recently been discovered that some, if not all, classical novae emit GeV gamma rays during outburst, but the mechanisms involved in the production of the gamma rays are still not well understood. We present here a comprehensive multi-wavelength dataset---from radio to X-rays---for the most gamma-ray luminous classical nova to-date, V1324 Sco. Using this dataset, we show that V1324 Sco is a canonical dusty Fe-II type nova, with a maximum ejecta velocity of 2600 km s$^{-1}$ and an ejecta mass of few $\times 10^{-5}$ M$_{\odot}$. There is also evidence for complex shock interactions, including a double-peaked radio light curve which shows high brightness temperatures at early times. To explore why V1324~Sco was so gamma-ray luminous, we present a model of the nova ejecta featuring strong internal shocks, and find that higher gamma-ray luminosities result from higher ejecta velocities and/or mass-loss rates. Comparison of V1324~Sco with other gamma-ray detected novae does not show clear signatures of either, and we conclude that a larger sample of similarly well-observed novae is needed to understand the origin and variation of gamma rays in novae.Comment: 26 pages, 13 figure

Perforated Meckel's diverticulum presenting with combined bowel and urinary obstruction and mimicking Crohn's disease: a case report

<p>Abstract</p> <p>Introduction</p> <p>Meckel's diverticulum is a common congenital anomaly of the gastrointestinal tract, but is an uncommon cause of serious complications in adults. Although cases of patients with hemorrhage, bowel obstruction or perforation associated with Meckel's diverticulum have been reported, there have been no prior reports of patients with combined urinary and bowel obstruction due to abscess formation.</p> <p>Case presentation</p> <p>We describe the case of a 21-year-old man with a history of recurrent papillary thyroid cancer, but no prior abdominal surgeries, who presented with a one-month history of rectal pain and new-onset obstipation with urinary retention. He reported night sweats and weight loss, and had a second-degree relative with known Crohn's disease. A digital rectal examination was notable and revealed marked tenderness with proximal induration. A computed tomography scan of the patient's abdomen revealed a large, complex, circumferential perirectal abscess compressing the rectal lumen and base of the urinary bladder, associated with terminal ileal thickening and an ileocecal fistula. A flexible sigmoidoscopy with an endorectal ultrasound scan displayed a complex abscess with extensive mucosal and surrounding inflammation. An exploratory laparotomy revealed a Meckel's diverticulum with a large perforation at its base, positioned near the ileocecal fistula and immediately superior to the perirectal abscess. The section of small bowel containing the Meckel's diverticulum, the terminal ileum, and the cecum, were all resected, and the abscess was debrided.</p> <p>Conclusions</p> <p>Pre-operative diagnosis of Meckel's diverticulum can be difficult. If the nature of the complication makes ultimate surgical management likely, an early laparoscopic or open exploration should be performed to prevent the morbidity and mortality associated with late complications.</p